1. Sporadic colorectal cancers with defective mismatch repair display a number of specific morphological characteristics: relationship between the expression of hMLH1 and hMSH2 proteins and clinicopathological features of 273 adenocarcinomas
- Author
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Anne Marie Bouvier, Jean Faivre, F Piard, L Martin, Tibor Ponnelle, N Mungra, Caroline Chapusot, C. Bonithon Kopp, and D Rageot
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Histology ,Stromal cell ,Base Pair Mismatch ,Adenocarcinoma ,Biology ,Pathology and Forensic Medicine ,Immunoenzyme Techniques ,Proto-Oncogene Proteins ,Biomarkers, Tumor ,medicine ,Carcinoma ,Humans ,Pathological ,Adaptor Proteins, Signal Transducing ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,Mucins ,Nuclear Proteins ,Microsatellite instability ,Anatomical pathology ,DNA, Neoplasm ,General Medicine ,Odds ratio ,Middle Aged ,medicine.disease ,digestive system diseases ,Neoplasm Proteins ,DNA-Binding Proteins ,MutS Homolog 2 Protein ,Immunohistochemistry ,Female ,DNA mismatch repair ,Stromal Cells ,Carrier Proteins ,Colorectal Neoplasms ,MutL Protein Homolog 1 ,Microsatellite Repeats - Abstract
Aims: The aim of this study was to assess the independent value of pathological criteria in the diagnosis of mismatch repair (MMR)-defective sporadic colorectal cancers. Methods and results: Resected colorectal adenocarcinomas (n = 273) were reviewed in order to identify a number of specific morphological features of MMR-defective carcinomas. Of the 273 cases, 35.2% were right-sided and 5.9% were poorly differentiated. Focal extracellular mucin secretion was seen in 5.1% of cases and a stromal follicular reaction in 4.6%. The expression of the two major MMR proteins hMLH1 and hMSH2 was studied by immunohistochemistry. Carcinomas were considered deficient in the MMR system when a loss of nuclear signal in neoplastic cells was observed for one of the proteins. Such an extinction was seen in 37 of the cases (13.6%). The hMLH1 protein was the one most frequently altered (86.5%). After multivariate analysis, three independent factors were significantly associated with MMR deficiency: proximal location [odds ratio (OR) = 9.30; 95% confidence interval (CI) 2.79, 30.98], the presence of a true stromal follicular reaction (OR = 13.60; 95% CI 2.98, 62.00) and poor differentiation (OR = 8.33; 95% CI 1.63, 40.32). Conclusions: These results confirm that sporadic colorectal MMR-defective adenocarcinomas display certain specific morphological characteristics. However, these pathological features are not sufficiently predictive and immunohistochemistry is needed to identify such tumours accurately.
- Published
- 2003
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